1. Musketeers Course October 20081 The Mucosal Immune System The organization of the mucosal immune systemThe organization of the mucosal immune system The mucosal response to infections and regulation of mucosal immune responsesThe mucosal response to infections and regulation of mucosal immune responses

2. Musketeers Course October 20082 The mucosal response to infection and regulation of mucosal immune responses

3. Musketeers Course October 20083 The mucosal response to infection and regulation of mucosal immune responses Many enteric pathogens need to exploit host mechanisms as part of their invasive strategies

4. Musketeers Course October 20084 Shigella flexneri infects intestinal epithelial cells triggering activation of the NFkB pathway The mucosal response to infection and regulation of mucosal immune responses

5. Musketeers Course October 20085 The mucosal response to infection and regulation of mucosal immune responses NOD: nucleotide binding oligomerization domain

6. Musketeers Course October 20086 The mucosal response to infection and regulation of mucosal immune responses Intestinal pathogens Bacteria Viruses Parasites induce inflammation

7. Musketeers Course October 20087 Entry of nonpathogenic antigens e.g. food proteins Mucosal Tolerance The mucosal response to infection and regulation of mucosal immune responses

8. Musketeers Course October 20088 The concept of mucosal tolerance. Prolonged mucosally administered antigens induce both systemic and mucosal unresponsiveness to the same Ag when challenged in the presence of adjuvant. The mucosal response to infection and regulation of mucosal immune responses 2 weeks later

9. Musketeers Course October 20089 The mucosal response to infection and regulation of mucosal immune responses Proposed dose- dependent mechanisms of oral tolerance.

10. Musketeers Course October 200810 The healthy intestine contains large quantities of bacteria but does not generate productive immunity against them The mucosal response to infection and regulation of mucosal immune responses Metabolism of dietary constituents Degrading toxins Produce vitamin K & short chain fatty acids Maintaining epithelium Compete the pathogens Inhibit pro-inflammatory signals

11. Musketeers Course October 200811 Clostridium difficile infection after treatment by antibiotics The mucosal response to infection and regulation of mucosal immune responses

12. Musketeers Course October 200812 The mucosal response to infection and regulation of mucosal immune responses Mucosal DC regulate the induction of tolerance and immunity

13. Musketeers Course October 200813 Commensal bacteria can prevent inflammatory responses in the intestine The mucosal response to infection and regulation of mucosal immune responses

14. Musketeers Course October 200814 Commensal bacteria  recognize by epithelial cells EC secretion of cytokines inhibit the expression of pro-inflammatory cytokines by DC and macrophage  DC & macrophages secrete signals for the expansion and/or survival of T cells with regulatory capacities, including regulatory T cells, T regulatory type 1 (TR1) cells, T helper 2 (TH2) cells and TH3 cells. The mucosal response to infection and regulation of mucosal immune responses

15. Musketeers Course October 200815 The mucosal response to infection and regulation of mucosal immune responses The mucosal immune system must maintain a balance between protective immunity and mucosal tolerance to a large number of different antigens

16. Musketeers Course October 200816 Celiac disease a breakdown of oral tolerance The mucosal response to infection and regulation of mucosal immune responses

17. Musketeers Course October 200817 The mucosal response to infection and regulation of mucosal immune responses Parasites Most helminths can induce both protective (Th2) and pathological (Th1) immune responses

18. Musketeers Course October 200818 The mucosal response to infection and regulation of mucosal immune responses Giardia lamblia Production of antibodies Infiltration of mucosa by effector cells

19. Musketeers Course October 200819 The mucosal response to infection and regulation of mucosal immune responses Cryptosporidium parvum & T. gondii Intracellular pathogens Require CD4Th1 and CD8 T cells to clear them

20. Musketeers Course October 200820 The mucosal response to infection and regulation of mucosal immune responses Chronic infections of intestinal helminths Production of mediators that dampen the innate immune responses Expression of decoy receptors of cytokines and chemokines Downregulation of IL-12 by DC  encourage generation of IL-10 producing Treg

21. Musketeers Course October 200821 The mucosal response to infection and regulation of mucosal immune responses Protective and pathological responses to intestinal helminths

22. Musketeers Course October 200822 The mucosal response to infection and regulation of mucosal immune responses

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